18 research outputs found
Simultaneous Delivery of Electrostatically Complexed Multiple Gene-Targeting siRNAs and an Anticancer Drug for Synergistically Enhanced Treatment of Prostate Cancer
Simultaneous
silencing of multiple apoptosis-related genes is an
attractive approach to treat cancer. In this article, we present a
multiple gene-targeting siRNA/drug delivery system for prostate cancer
treatment with a high efficiency. Bcl-2, survivin, and androgen receptor
genes involved in the cell apoptosis pathways were chosen as silencing
targets with three different siRNAs. The colloidal nanocomplex delivery
system (<10 nm in size) was formulated electrostatically between
anionic siRNAs and a cationic drug (BZT), followed by encapsulation
with the Pluronic F-68 polymer. The formulated nanocomplex system
exhibited sufficient stability against nuclease-induced degradation,
leading to successful intracellular delivery for the desired therapeutic
performance. Silencing of targeted genes and apoptosis induction were
evaluated in vitro on human prostate LNCaP-LN3 cancer cells by using
various biological analysis tools (e.g., real-time PCR, MTT cell viability
test, and flow cytometry). It was demonstrated that when the total
loaded siRNA amounts were kept the same in the nanocomplexes, the
simultaneous silencing of triple genes with co-loaded siRNAs (i.e.,
Bcl-2, survivin, and AR-targeting siRNAs) enhanced BZT-induced apoptosis
of cancer cells more efficiently than the silencing of each single
gene alone, offering a novel way of improving the efficacy of gene
therapeutics including anticancer drug
MRI Monitoring of Tumor-Selective Anticancer Drug Delivery with Stable Thermosensitive Liposomes Triggered by High-Intensity Focused Ultrasound
Monitoring of drug release from a
heat-activated liposome carrier
provides an opportunity for real-time control of drug delivery and
allows prediction of the therapeutic effect. We have developed short-chain
elastin-like polypeptide-incorporating thermosensitive liposomes (STLs).
Here, we report the development of STL encapsulating gadobenate dimeglumine
(Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL).
The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL;
however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL.
MRI studies showed that the difference in T<sub>1</sub> relaxation
time between 37 and 42 °C for Gd-Dox-STL was larger than the
difference for Gd-Dox-LTSL. Although relaxivity for both liposomes
at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C
was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to
Gd-BOPTA leakage from the LTSL because of low stability at 37 °C.
Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95
h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with <i>in vitro</i> stability data. <i>In vivo</i> MRI experiments
demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia
induced by high-intensity focused ultrasound (HIFU), which suggests
STL is a promising tumor selective formulation when coupled with MR-guided
HIFU
Fabrication of Protease-Sensitive and Light-Responsive Microcapsules Encompassed with Single Layer of Gold Nanoparticles by Using Self-Assembly Protein of α‑Synuclein
A bioapplicable cargo delivery system
requires the following characteristics
of biocompatibility, in vivo stability, and selective cargo release
at target sites. We introduce herein the microcapsules enclosed with
a single-layered shell of gold nanoparticles (AuNPs) mutually connected
by an amyloidogenic protein of α-synuclein (αS). The microcapsules
were fabricated by producing oilÂ(chloroform)-in-water Pickering emulsions
of the αS-encapsulated AuNPs and subsequent molecular engagement
of the outlying αS molecules, leading to formidable β-sheet
formation in the presence of chloroform. The wrinkled skin of microcapsules
obtained after evaporation of the internal chloroform also reflects
robustness of the protein–protein interaction, which was experimentally
confirmed by their rheological stability. For the emulsions loaded
with rhodamine 6G, their dye release was demonstrated to be controlled
by proteases. Along with their photothermal activity, the AuNP-containing
microcapsules and their proteolyzed fragments were therefore suggested
to be capable of eliminating aberrant cells in the protease-activated
pathologically affected areas. Orthogonal cargo loading was also achieved
by encapsulating both hydrophobic and hydrophilic substances either
directly dissolved in chloroform or prepackaged in inverted micelles,
respectively. Microcapsule’s functionality was further expanded
by localizing quantum dots, magnetic nanoparticles, and antibodies
inside or on the surface of the microcapsules. Taken together, these
multimodal AuNP microcapsules are suggested to be an ideal cargo carrier
system, which could be employed in not only biomedical theranostic
applications as they exhibit structural robustness, specific targeting,
triggered release, and photothermal activity but also sensor development
in general
MFK902 inhibition of NIH3T3 cell adhesion and migration.
<p>βig-h3-derivatives, including RGD (GGRGDSP), MFK00, and MFK902 peptides, were prepared as described in the Methods section. Inhibition of adhesion by (A) the RGD and RGE, (B) MFK00, and (C) MFK902 peptides. Inhibition of migration by (D) the RGD and RGE, (E) MFK00, and (F) MFK902 peptides. *<i>p</i> < 0.05. Values are presented as the mean ± SEM.</p
<i>In vivo</i> safety profile in CIA mice treated with MFK902.
<p><i>In vivo</i> safety profile in CIA mice treated with MFK902.</p
Modulation of clinical arthritis in mice with collagen-induced arthritis (CIA) after MFK902 treatment.
<p>(A) Distribution of Cy5.5-labeled MFK902 in the mice with active CIA. MFK902-Cy5.5 or free Cy5.5 were intravenously injected into mice and then near-infrared fluorescence (NIRF) images were captured using an eXplore Optix system. Representative color-coded images and total photon counts (mean at ± SD) indicated times are shown. (B-C) Mice with CIA were treated intraperitoneally with MFK902 daily at indicated doses, methotrexate (MTX, 1 mg/kg twice weekly), or phosphate-buffered saline (Control) beginning on day 23 after the first immunization. Arthritis scores are shown for 7–8 mice per group. (B) Clinical arthritis index. (C) Incidence of paw involvement. *<i>p</i> < 0.05. Data are expressed as the mean ± SEM.</p
<i>In vivo</i> safety profile in CIA mice treated with MFK902.
<p><i>In vivo</i> safety profile in CIA mice treated with MFK902.</p
Ultrafast Nanoimaging of the Photoinduced Phase Transition Dynamics in VO<sub>2</sub>
Many phase transitions in correlated
matter exhibit spatial inhomogeneities
with expected yet unexplored effects on the associated ultrafast dynamics.
Here we demonstrate the combination of ultrafast nondegenerate pump–probe
spectroscopy with far from equilibrium excitation, and scattering
scanning near-field optical microscopy (<i>s</i>-SNOM) for
ultrafast nanoimaging. In a femtosecond near-field near-IR (NIR) pump
and mid-IR (MIR) probe study, we investigate the photoinduced insulator-to-metal
(IMT) transition in nominally homogeneous VO<sub>2</sub> microcrystals.
With pump fluences as high as 5 mJ/cm<sup>2</sup>, we can reach three
distinct excitation regimes. We observe a spatial heterogeneity on
∼50–100 nm length scales in the fluence-dependent IMT
dynamics ranging from <100 fs to ∼1 ps. These results suggest
a high sensitivity of the IMT with respect to small local variations
in strain, doping, or defects that are difficult to discern microscopically.
We provide a perspective with the distinct requirements and considerations
of ultrafast spatiotemporal nanoimaging of phase transitions in quantum
materials
Downregulation of inflammatory mediators after MFK902 treatment in the arthritis tissues from CIA mice.
<p>(A) Semi-quantitative measurement of inflammatory mediators from joint tissues using reverse transcription-polymerase chain reaction (RT-PCR). The comparison of transcript levels was performed using 18S ribosomal RNA as the denominator and normalized according to the relative expression level of inflammatory mediators from non-arthritic mice. (B) Immunoblot analysis of ICAM-1 and RANKL expression. *<i>p</i> < 0.05 vs. controls. Values are expressed as the mean ± SEM. CCL2, chemokine (C-C motif) ligand 2; ICAM-1, intercellular adhesion molecule-1; RANKL, Receptor activator of nuclear factor kappa-B ligand; VCAM-1, vascular cell adhesion molecule-1.</p
Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation
Optically active nanomaterials have
shown great promise as a nanomedicine
platform for photothermal or photodynamic cancer therapies. Herein,
we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA)
for photothermally boosted photodynamic tumor ablation. Unlike other
supramolecular gold constructs based on gold nanoparticle building
blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan
conjugates as a drug carrier for a hydrophobic photodynamic therapy
agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold
upon which gold can grow. Gold nanoclusters were selectively installed
on the outer shell of the hyaluronan nanoassembly, forming a gold
shell. Given the dual protection effect by the hyaluronan self-assembly
as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA
(Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream.
Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA
were considerably quenched due to the gold nanoclusters covering the
surface of the nanoassemblies; however, photothermal activation by
808 nm laser irradiation induced a significant increase in temperature,
which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence
and photodynamic effects were recovered far more rapidly in cancer
cells due to certain intracellular enzymes, particularly hyaluronidases
and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors
both <i>in vitro</i> and <i>in vivo</i>. Tumors
were completely ablated with a 100% survival rate and complete skin
regeneration over the 50 days following Vp-GNc-HyNA treatment in an
orthotopic breast tumor model. Our results suggest that photothermally
boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent
therapeutic means to eradicate tumors